Pharmacogenomics, the study of the effect of genetics on the variation in drug response, is designed to maximize drug efficacy and minimize adverse effects. It is assuming increasing importance in ...clinical practice. Rheumatologists, who manage patients with complex diseases with unpredictable outcomes over long periods of time, should embrace tools that help customize treatment for their patients. In this article, the basis for pharmacogenomics is presented, followed by description of the tests relevant to drugs encountered in rheumatology practice, concluding with ideas about implementation and future developments.
Major depressive disorder (MDD) is a very common stress-related mental disorder that carries a huge burden for affected patients and the society. It is associated with a high mortality that derives ...from suicidality and the development of serious medical conditions such as heart diseases, diabetes, and stroke. Although a range of effective antidepressants are available, more than 50% of the patients do not respond to the first treatment they are prescribed and around 30% fail to respond even after several treatment attempts. The heterogeneous condition of MDD, the lack of biomarkers matching patients with the right treatments and the situation that almost all available drugs are only targeting the serotonin, norepinephrine, or dopamine signaling, without regulating other potentially dysregulated systems may explain the insufficient treatment status. The hypothalamic-pituitary-adrenal (HPA) axis is one of these other systems, there is numerous and robust evidence that it is implicated in MDD and other stress-related conditions, but up to date there is no specific drug targeting HPA axis components that is approved and no test that is routinely used in the clinical setting identifying patients for such a specific treatment. Is there still hope after these many years for a breakthrough of agents targeting the HPA axis? This review will cover tests detecting altered HPA axis function and the specific treatment options such as glucocorticoid receptor (GR) antagonists, corticotropin-releasing hormone 1 (CRH
) receptor antagonists, tryptophan 2,3-dioxygenase (TDO) inhibitors and FK506 binding protein 5 (FKBP5) receptor antagonists.
Digital Twins for Multiple Sclerosis Voigt, Isabel; Inojosa, Hernan; Dillenseger, Anja ...
Frontiers in immunology,
05/2021, Volume:
12
Journal Article
Peer reviewed
Open access
An individualized innovative disease management is of great importance for people with multiple sclerosis (pwMS) to cope with the complexity of this chronic, multidimensional disease. However, an ...individual state of the art strategy, with precise adjustment to the patient's characteristics, is still far from being part of the everyday care of pwMS. The development of digital twins could decisively advance the necessary implementation of an individualized innovative management of MS. Through artificial intelligence-based analysis of several disease parameters - including clinical and para-clinical outcomes, multi-omics, biomarkers, patient-related data, information about the patient's life circumstances and plans, and medical procedures - a digital twin paired to the patient's characteristic can be created, enabling healthcare professionals to handle large amounts of patient data. This can contribute to a more personalized and effective care by integrating data from multiple sources in a standardized manner, implementing individualized clinical pathways, supporting physician-patient communication and facilitating a shared decision-making. With a clear display of pre-analyzed patient data on a dashboard, patient participation and individualized clinical decisions as well as the prediction of disease progression and treatment simulation could become possible. In this review, we focus on the advantages, challenges and practical aspects of digital twins in the management of MS. We discuss the use of digital twins for MS as a revolutionary tool to improve diagnosis, monitoring and therapy refining patients' well-being, saving economic costs, and enabling prevention of disease progression. Digital twins will help make precision medicine and patient-centered care a reality in everyday life.
During the last years, an extraordinary effort has been made to identify biomarkers as potential tools for improving prevention, diagnosis, drug response and drug development in psychiatric ...disorders. Contrary to other diseases, mental illnesses are classified by diagnostic categories with a broad variety list of symptoms. Consequently, patients diagnosed from the same psychiatric illness present a great heterogeneity in their clinical presentation. This fact together with the incomplete knowledge of the neurochemical alterations underlying mental disorders, contribute to the limited efficacy of current pharmacological options. In this respect, the identification of biomarkers in psychiatry is becoming essential to facilitate diagnosis through the developing of markers that allow to stratify groups within the syndrome, which in turn may lead to more focused treatment options. In order to shed light on this issue, this review summarizes the concept and types of biomarkers including an operational definition for therapeutic development. Besides, the advances in this field were summarized and sorted into five categories, which include genetics, transcriptomics, proteomics, metabolomics, and epigenetics. While promising results were achieved, there is a lack of biomarker investigations especially related to treatment response to psychiatric conditions. This review includes a final conclusion remarking the future challenges required to reach the goal of developing valid, reliable and broadly-usable biomarkers for psychiatric disorders and their treatment. The identification of factors predicting treatment response will reduce trial-and-error switches of medications facilitating the discovery of new effective treatments, being a crucial step towards the establishment of greater personalized medicine.
Clinical implementation of tumor organoids for personalized medicine requires that pure tumor organoids can be reliably established. Here, we present our experience with organoid cultures from >70 ...non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to identify tumor purity of organoids established from intrapulmonary tumors. Eighty percent of organoids from intrapulmonary lesions have a normal copy number profile, suggesting overgrowth by normal airway organoids (AOs). This is further supported by the failure to detect mutations found in the original tumor in organoids. Histomorphology alone is insufficient to determine tumor purity, but when combined with p63 immunostaining, tumor and normal AOs can be distinguished. Taking into account overgrowth by normal AOs, the establishment rate of pure NSCLC organoids is 17%. Therefore, current methods are insufficient to establish pure NSCLC organoids from intrapulmonary lesions. We discourage their use unless steps are taken to prevent overgrowth by normal AOs.
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•Frequent overgrowth of lung cancer organoids by normal airway organoids•Copy number profiling and IHC can be used to distinguish tumor and normal organoids•Low establishment rate of pure lung cancer organoids limits their clinical utility
Using a combination of genetic analyses and immunohistochemistry, Dijkstra et al. find that the majority of organoids derived from intrapulmonary lung cancers are overgrown by normal airway organoids. This limits the overall establishment rate of pure lung cancer organoids to 17%, restricting their utility for personalized medicine.
•Survey of the applications of Reinforcement Learning (RL) in healthcare domains.•Identification of seven categories with respect to the most relevant field of applications of RL approaches in ...medicine.•A brief discussion to highlight some considerations that can be taken in account when new prediction models get defined in the field of precision medicine.•Analysis of the distribution of the surveyed solutions with respect to their category, adopted Reinforcement Learning approaches, their impact in terms of citations, and publication year.•Group the healthcare domains in seven classes of application and for each one stating an overview of the application of Reinforcement-Learning-based approach.
Discovering new treatments and personalizing existing ones is one of the major goals of modern clinical research. In the last decade, Artificial Intelligence (AI) has enabled the realization of advanced intelligent systems able to learn about clinical treatments and discover new medical knowledge from the huge amount of data collected. Reinforcement Learning (RL), which is a branch of Machine Learning (ML), has received significant attention in the medical community since it has the potentiality to support the development of personalized treatments in accordance with the more general precision medicine vision. This report presents a review of the role of RL in healthcare by investigating past work, and highlighting any limitations and possible future contributions.
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It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with ...different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms.
Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year. With the new understanding of the ...molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients' disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient's physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.
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